biostudies-literatureUnknown26(2)Sevrin TCellular utilization of available energy flows to drive a multitude of forms of cellular "work" is a major biological constraint. Cells steer metabolism to address changing phenotypic states but little is known as to how bioenergetics couples to the richness of processes in a cell as a whole. Here, we outline a whole-cell energy framework that is informed by proteomic analysis and an energetics-based gene ontology. We separate analysis of metabolic supply and the capacity to generate high-energy phosphates from a representation of demand that is built on the relative abundance of ATPases and GTPases that deliver cellular work. We employed mouse embryonic fibroblast cell lines that express wild-type KRAS or oncogenic mutations and with distinct phenotypes. We observe shifts between energy-requiring processes. Calibrating against Seahorse analysis, we have created a whole-cell energy budget with apparent predictive power, for instance in relation to protein synthesis.iScience105931https://www.ebi.ac.uk/biostudies/studies/S-EPMC9874014biostudies-literatureWhole-cell energy modeling reveals quantitative changes of predicted energy flows in RAS mutant cancer cell lines.PMC9874014Ternet CJunk PWynne KCaffarini MPrins SLuthert PJKiel CCatozzi SStrasser LSevrin TD'Arcy COliviero GfalseWhole-cell energy modeling reveals quantitative changes of predicted energy flows in RAS mutant cancer cell lines.Cellular utilization of available energy flows to drive a multitude of forms of cellular "work" is a major biological constraint. Cells steer metabolism to address changing phenotypic states but little is known as to how bioenergetics couples to the richness of processes in a cell as a whole. Here, we outline a whole-cell energy framework that is informed by proteomic analysis and an energetics-based gene ontology. We separate analysis of metabolic supply and the capacity to generate high-energy phosphates from a representation of demand that is built on the relative abundance of ATPases and GTPases that deliver cellular work. We employed mouse embryonic fibroblast cell lines that express wild-type KRAS or oncogenic mutations and with distinct phenotypes. We observe shifts between energy-requiring processes. Calibrating against Seahorse analysis, we have created a whole-cell energy budget with apparent predictive power, for instance in relation to protein synthesis.2023-01-01T00:00:00Z2023 Feb2025-04-26T13:19:47.994Z2025-04-06T14:10:39.827ZS-EPMC98740143671124610.1016/j.isci.2023.105931